CO2enhances the ability ofCandida albicansto form biofilms, overcome nutritional immunity and resist antifungal treatment

Abstract

AbstractC. albicansis the predominant fungal pathogen of humans and frequently colonises medical devices, such as voice prosthesis, as a biofilm. It is a dimorphic yeast that can switch between yeast and hyphal forms in response to environmental cues, a property that is essential during biofilm establishment and maturation. One such cue is the elevation of CO2levels, as observed in exhaled breath.. However, despite the clear medical relevance, the effects of CO2onC. albicansbiofilm growth has not been investigated to date. Here, we show that physiologically relevant CO2elevation enhances each stage of theC. albicansbiofilm forming process;from attachment through to maturation and dispersion.. The effects of CO2are mediated via the Ras/cAMP/PKA signalling pathway and the central biofilm regulators Efg1, Brg1, Bcr1 and Ndt80. Biofilms grown under elevated CO2conditions also exhibit increased azole resistance, tolerance to nutritional immunity and enhanced glucose uptake to support their rapid growth. These findings suggest thatC. albicanshas evolved to utilise the CO2signal to promote biofilm formation within the host. We investigate the possibility of targeting CO2activated processes and propose 2-Deoxyglucose as a drug that may be repurposed to preventC. albicansbiofilm formation on medical airway management implants. We thus characterise the mechanisms by which CO2promotesC. albicansbiofilm formation and suggest new approaches for future preventative strategies.